Herman Eugene, Eldridge Sandy
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892 USA.
Cardiooncology. 2019 Jun 3;5:6. doi: 10.1186/s40959-019-0040-y. eCollection 2019.
The search for new chemical entities which are clinically effective and do not adversely affect the cardiovascular system is an ongoing objective. In vivo studies designed to detect potential drug-induced cardiovascular toxicity typically utilize both rodent and non-rodent species. An important component of such studies includes the microscopic evaluation of tissues for histopathologic changes. A factor which could potentially complicate this type of evaluation relates to the potential for laboratory animals to develop natural or spontaneous pathological cardiovascular lesions. Some types of these naturally occurring alterations are similar to those induced by chemical compounds and thus could confound accurate interpretation. Accurate morphologic analysis becomes contingent upon the ability to distinguish spontaneous cardiovascular changes from actual drug-induced lesions. A summary of some of the more frequently reported spontaneous cardiovascular alterations in commonly-used laboratory animals is presented below. Special emphasis is given to the spectrum of spontaneous background myocardial pathology that might be encountered during preclinical studies conducted to identify potential cardiotoxic actions of anticancer agents.
寻找临床有效且不会对心血管系统产生不利影响的新化学实体是一个持续的目标。旨在检测潜在药物诱导的心血管毒性的体内研究通常会使用啮齿动物和非啮齿动物物种。此类研究的一个重要组成部分包括对组织进行显微镜检查以发现组织病理学变化。可能使这种评估复杂化的一个因素是实验动物出现自然或自发病理性心血管病变的可能性。这些自然发生的改变中的某些类型与化合物诱导的改变相似,因此可能会混淆准确的解释。准确的形态学分析取决于区分自发心血管变化与实际药物诱导病变的能力。以下列出了一些常用实验动物中更频繁报告的自发心血管改变。特别强调了在进行临床前研究以确定抗癌药物潜在心脏毒性作用时可能遇到的自发背景心肌病理学范围。